Mo Nianchun,Cai Xi,Xie Shuqin,Zhong Ling.Role of calcitriol on epithelial-mesenchymal transition of NRK52E cells induced by advanced glycation end products[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(15):1735-1740.
Mo Nianchun,Cai Xi,Xie Shuqin,Zhong Ling.Role of calcitriol on epithelial-mesenchymal transition of NRK52E cells induced by advanced glycation end products[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(15):1735-1740.DOI:
Role of calcitriol on epithelial-mesenchymal transition of NRK52E cells induced by advanced glycation end products
目的 探讨骨化三醇对晚期糖基化终末产物(advanced glycation end products,AGEs)诱导的肾小管上皮细胞间质转化(epithelial-mesenchymal transition,EMT)的作用及可能机制。 方法 先单独用骨化三醇刺激细胞,再采用AGEs处理NRK52E细胞,建立由AGEs诱导的细胞EMT模型。分为4组:对照组、模型组、低剂量骨化三醇(10nmol/L)预处理的模型组、高剂量骨化三醇(100nmol/L)预处理的模型组。利用Western blot、逆转录实时定量PCR等方法检测E-cadherin、α-SMA、AGEs特异性受体(receptor for advanced glycation end products
Objective To investigate the role of calcitriol on advanced glycation end products (AGEs) induced epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells and explore the possible mechanism. Methods NRK52E cells were pretreated with calcitriol and divided into 4 groups upon the addition of AGEs
i.e.
control group
AGEs group
AGEs groups pretreated with low (10 nmol/L) and high (100 nmol/L) concentration of calcitriol. The expression of E-cadherin
alpha smooth muscle actin (α-SMA)
receptor for AGE (RAGE) and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by Western blotting and reverse real-time quantitative polymerase chain reaction (RT-PCR). Results Calcitriol alone had no obvious effect on the expression of E-cadherin and α-SMA in rat renal tubular epithelial cells. AGEs down-regulated E-cadherin and up-regulated α-SMA in comparison to the control. AGEs also enhanced the expression of RAGE and phosphorylation of NF-κB. Calcitriol could significantly reverse all the aforementioned effects induced by AGEs (P0.05). When treated with anti-RAGE antibody AF1616
AGEs-induced reduction in E-cadherin and increase in α-SMA were inhibited. Furthermore
NF-κB inhibitor IMD0354 partly attenuated AGEs-induced up-regulation of RAGE via inhibition of calcitriol. Conclusion Mechanistically
calcitriol suppresses EMT in renal tubular epithelial cells through downregulation of RAGE and blockage of NF-κB phosphorylation.